We propose to use our established Neuropathology Core facilities at the Institute of Neurological Sciences at the Southern General Hospital, University of Glasgow, to facilitate and support the investigations of the University of Pennsylvania Head Injury Center into the molecular and cellular mechanisms of cellular injury and death following traumatic brain injury (TBI). We have been supported by the UPHIC Program Project grant for over 15 years and in the current application, we propose to: (1) Secure, preserve, examine and genotype brain tissue from fatally head- injured patients admitted to the managed by the Department of Neurosurgery, Glasgow (Professor G.M. Teasdale). Material from age/sex matched controls will be secured and similarly processed. This tissue, together with frozen material from human autopsy cases from our brain bank will be made available to the Investigators of Projects 1, 2 and 3 to enable them to perform cross-species comparisons and make a direct correlation of the pathobiological mechanisms of cellular death and dysfunction between animal models and humans subjects to TBI. (2) Our Core will also provide and perform the detailed histopathological assessment of the extent and pattern of cell death following experimental brain injury (in conjunction with Project 1) and evaluate the ability of novel neuroprotective strategies to protect cells following brain injury and treatment with experiment compounds (in conjunction with Project 5). (3) Finally, we will perform the morphological assessment of apoptotic/necrotic cell death in human brain-injured tissue which will be directly compared with similar patterns following experimental TBI (in conjunction with Project 3). Our expertise in neuropathological assessment following TBI will provide us with the unique opportunity to evaluate the clinical fidelity of the experimental brain injury models associated with this grant (side-by-side comparisons between animal and human tissue), and to insure the accurate histological evaluation of novel neuroprotective therapies for brain injury.